tbuckley/cabot-search huggingface dataset:
Resection of primary colon cancer with and without resection of liver metastases: Propensity-score matched analysis.
Authors: Sameh Hany Emile, Nir Horesh, Zoe Garoufalia, Rachel Gefen, Peige Zhou, Steven D Wexner
Journal: Journal of Clinical Oncology (2023)

e15580 Background: Studies show that attempts to treat liver metastases during or before primary colonic cancer resection may improve survival. We aimed to compare overall survival of patients with colon cancer and liver metastases who underwent primary tumor resection with/without resection of liver metastases. Methods: This retrospective cohort study included patients with stage IV colon adenocarcinoma and isolated liver metastases who underwent surgical resection, using data from the National Cancer Database between 2015-2019. Patients with metastases to other organs or who did not have primary tumor resection were excluded. The cohort was divided into Colectomy-only (resection of primary colonic cancer only) and Colectomy-plus (resection of primary tumor and liver metastases) groups. After comparing, significant baseline and treatment confounders were identified and groups were matched using the nearest neighbor, 1:1 propensity-score method. Primary outcome was overall survival; secondary endpoints were short-term mortality and 30-day unplanned readmission. Results: 6780 patients who underwent primary tumor only resection and 4082 who underwent primary tumor and liver metastases resection were included. Patients in the Colectomy-only group were significantly older (63.73±13.59 vs 59.56±13.32 years;p &lt; 0.001), more often male (56% vs 53.5%;p = 0.01), had more comorbidities (Charlson score 3: 4.4% vs 3.3%;p = 0.001) and right-sided colonic cancer (45.7% vs 43.2%;p = 0.002), shorter time before surgery (10 vs 30 days;p &lt; 0.001), and more laparoscopic surgery (40.4% vs 35%;p &lt; 0.001). Colectomy-only group patients had less chemotherapy (48.6% vs 50.7%, p = 0.04) and immunotherapy (34.1% vs 40.6%, p &lt; 0.001) whereas Colectomy-plus group patients had more neoadjuvant systemic therapy (18.8% vs 10.2%;p &lt; 0.001). Median overall survival of the Colectomy-plus group was significantly longer than Colectomy-only group (45.1 vs 24.4 months; p &lt; 0.001). After matching for significant confounders, 2038 patients were included in each group. There were no significant differences between the two groups in 30-day (3.8% vs 3.1%;p = 0.3) and 90-day mortality (7.7% vs 6.6%;p = 0.2). Colectomy-plus group patients had significantly higher 30-day unplanned readmissions (7.2% vs 5.3%, p = 0.02) and significantly longer median overall survival (41.5 vs 28.4 months, p &lt; 0.001). On Cox-regression analysis, resection of liver metastases and primary colonic tumor was associated with 33% mortality reduction (HR: 0.678, 95%CI: 0.618-0.745, p &lt; 0.001). Conclusions: Resection of colonic cancer liver metastasis with the primary tumor is associated with significant survival benefit and may prolong survival by approximately 12 months, versus primary tumor resection alone. Synchronous resection of the primary tumor and liver metastases should be considered as it appears to offer survival benefit.
Generalizable FGFR prediction across tumor types using self supervised learning.
Authors: Chaitanya Parmar, Albert Juan Ramon, Nicole L. Stone, Spyros Triantos, Joel Greshock, Kristopher Standish
Journal: Journal of Clinical Oncology (2023)

e15057 Background: Deep Learning models have demonstrated the ability to detect tumors, classify disease state, or infer genetic biomarkers from digital whole slide images (WSI) of Hematoxylin and Eosin (H&amp;E)-stained tissue. Such models can be deployed to improve clinical practice or efficiently recruit for clinical trials. However, the data to train these models is often very limited and image capture protocols vary between labs. We propose to use Self Supervised Learning (SSL) on large unlabeled histopathology data sets to improve generalizability and predictive performance of deep learning models on unseen data. Methods: We pre-trained a Convolutional Neural Network (CNN) using SSL on 25,120 unlabeled, digital WSIs from various sources (multiple scanners, hospital systems, labs, diseases, tissue sites). We then fine-tuned the pre-trained CNN to infer the presence or absence of select FGFR alterations in Muscle Invasive Bladder Cancer (MIBC) from the digital WSI. We applied this model (FGFR SSL ) to WSIs of biopsies from other data sources and tumor types and compared with a model (FGFR TRAD ) that was trained exclusively on MIBC samples without self-supervised learning. Results: The FGFR SSL model achieved an Area Under ROC Curve (AUC = 0.80) on MIBC WSIs and maintained performance on images from an independent lab (AUC=0.82). We further show that the model generalizes to Non-Muscle Invasive Bladder Cancer (NMIBC) samples with (AUC = 0.76) and Pan-Tumor WSIs (AUC: 0.83). The FGFR TRAD model trained without SSL-based pre-training achieved an Area Under ROC Curve (AUC: 0.76) on MIBC WSIs was less generalizable, showing lower performance for independent data (AUC = 0.72), NMIBC samples (AUC = 0.72), and Pan-Tumor samples (AUC = 0.64). Conclusions: We leveraged SSL pretraining to improve the reliability and generalizability of AI-based models across multiple data sources. We also demonstrate our model’s ability to infer FGFR status across multiple solid tumor types after training on only MIBC samples, suggesting the cell morphology conferred by FGFR alteration in cancer may be shared across diverse tumor types. These models represent a means for efficiently screening patients for actionable clinical biomarkers in a robust manner to guide clinical decisions and inform drug development efforts. [Table: see text]
Analysis of short-term efficacy and safety of mitoxantrone hydrochloride liposome regimen therapy in adult acute myeloid leukemia.
Authors: Jun Ma, Junbin Hu, Li Liu, Yuqing Chen, Aili He, Shifeng Lou, Jian Ge, Kunming Qi, Yanli Yang, Jingjing Ye, Hai Cheng, Yinghao Lu, Linhui Wang, Huili Cai, Xudong Wei, Xiangdong Yang, Hua Xue, Hongxiang Wang
Journal: Journal of Clinical Oncology (2023)

7039 Background: Acute myeloid leukemia (AML) is highly heterogeneous, and more than half of patients (pts) will experience refractory or relapse, with poor prognosis. Currently, chemotherapy and hematopoietic stem cell transplantation (HSCT) are the main treatments for AML. Mitoxantrone is a synthetic anthracenedione anti-cancer drug that is effective in lymphoma, leukemia, and other solid tumors. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics and significantly prolong the survival time of animals compared with the same dose of mitoxantrone (Li 2008). However, there is still a lack of systematic reports about the real-world application of PLM60 in AML. Methods: We performed a multicenter retrospective analysis of 82 pts with newly diagnosed AML and relapsed/refractory (R/R) AML, who received at least one cycle of PLM60 regimen between January 2022 and November 2022. Pts aged 18 years and above with confirmed diagnosis of AML according to the 2016-revised WHO criteria were eligible for inclusion, except acute promyelocytic leukemia (APL). The median dose of PLM60 in the regimen was 20.0 (range 10.3–31.6) mg/m 2 . Efficacy was assessed by composite complete remission (CRc) rate and overall response rate (ORR), and logistic regression analysis was performed to analyze factors affecting the curative effect. Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: 82 pts were enrolled with a median age of 50.5 (range 20-83) years. There were 71 cases of de novo AML and 11 cases of secondary AML. Targeted sequencing was performed on 86.6% of pts (71/82). FLT3 was the most commonly mutated gene found in 22.5% (16/71), followed by ASXL1 mutated in 12.7%, NPM1 in 11.3%, and TP53 in 11.3%. 4.9% (4/82) of pts underwent HSCT. Among the 25 newly diagnosed pts, CRc rate was 72.0% (18/25) and ORR was 92.0% (23/25). Among the 57 R/R pts, CRc rate was 24.6% (14/57) and ORR was 40.4% (23/57). The courses of induction failure ( OR= 16.617, P= 0.026), and the duration of the first complete remission (CR1) ( OR= 20.647, P= 0.007) were independent influencing factors of the efficacy. Common grade 3/4 AEs included decreased neutrophil count (84.1%), thrombocytopenia (76.8%), anemia (73.2%), febrile neutropenia (47.6%), pulmonary infection (11.0%) and upper respiratory tract infection (2.4%). The overall safety was acceptable and controllable. Conclusions: The PLM60 regimen had an encouraging efficacy and showed a manageable safety profile with the most adverse events being hematologic toxicities.
Uterine sarcoma patients who underwent morcellation: Who are they? Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA- NOGGO RU1).
Authors: Eva Roser, Rebecca Mirbach, Peter Reichardt, Dario Zocholl, Maximillian Klar, Philipp Harter, Stefan Kommoss, Uwe Andreas Ulrich, Alexander Mustea, Pauline Wimberger, Michael Weigel, Matthias Frank, Barbara Schmalfeldt, Lars Ch. Hanker, Anne Flörcken, Tjadina Arndt, Klaus Pietzner, Jalid Sehouli
Journal: Journal of Clinical Oncology (2023)

e17632 Background: Uterine sarcomas represent a group of rare malignant mesenchymal neoplasms with most types of them being associated with poor prognosis. In clinical practice, it is challenging to distinguish them from the most common benign tumors in women, so-called leiomyomas. Due to erroneous diagnosis, there is a risk of morcellating an occult sarcoma. This often leads to the distribution of malignant tissue in the abdominal cavity and a worse prognosis in most of the patients. In order to better understand this high-risk group of patients we analyzed their characteristics and management based on data of the real-world German registry for gynecological sarcoma (REGSA). Methods: REGSA is a real-world multicenter prospective registry including patients with gynecologic sarcomas in the primary and the recurrent situation of disease. For this work, we performed a descriptive analysis with data from all available patients with documented morcellation of uterine sarcoma. Results: 8.7% (n=76) of a total of 874 patients (registration period 09/2015-05/2022) were morcellated. Those 76 patients had a median age of 50.5 years. Thirty-seven patients (48.7%) were ≥50 years of age at the time of surgery. Leiomyosarcoma was the most common histopathological subtype (n=42; 50.3%). Fifty-eight patients (76.3%) had laparoscopic operations. A subtotal hysterectomy was the most common procedure used in 40.8% (n=31). Diagnostic curettage was performed in 5.3% of all cases (n=4). The predominant preoperative symptom was "bleeding disorders" in 19 patients (25.0%). Follow-up treatment after morcellation was heterogeneous. 17 patients received chemotherapy, with docetaxel and gemcitabine being the most frequently used regimen (n=8; 47.1%), followed by combinations with anthracyclines in 5 patients (29.4%). Conclusions: Many patients were over 50 years of age at the time of morcellation, although it is undisputed that the risk of morcellating occult uterine sarcoma increases with age. Whether curettage has diagnostic value needs to be further investigated. There is a high clinical need to define a consensus on further management of this high-risk group, regarding adjuvant therapy and follow-up care for there seems to be a great deal of uncertainty regarding adjuvant management.
Impact of number and size of colorectal metastases (CRM) on survival in patients with<i> RAS</i> wild-type metastatic colorectal cancer treated within the PanaMa trial (AIO KRK 0212).
Authors: Greta Sommerhäuser, Annika Kurreck, Alexander Beck, Uli Fehrenbach, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Lothar Mueller, Alexander Koenig, Ludwig Fischer Von Weikersthal, Johanna Wanda Meyer-Knees, Alexej Ballhausen, Arndt Stahler, Volker Heinemann, Swantje Held, Annabel Helga Sophie Alig, Stefan Kasper, Sebastian Stintzing, Tanja Trarbach, Dominik Paul Modest
Journal: Journal of Clinical Oncology (2023)

3551 Background: In this exploratory analysis, we aim to evaluate surrogates of metastatic burden, namely number of CRMs and size of largest CRM, for their prognostic and predictive value on efficacy of maintenance therapy with 5-fluorouracil/leucovorin (FU/FA) plus panitumumab (pmab) or FU/FA alone in RAS wildtype mCRC patients treated within the PanaMa trial. Methods: Number of CRMs and size of largest CRM at baseline were determined taking into account target and non-target lesions measured by central radiological review. Median number of metastases was set as threshold (n≤/ &gt; 10) to assess the prognostic and predictive value of CRM count on PFS and OS of maintenance therapy. A threshold of ≤/ &gt; 50mm was set to evaluate the impact of the largest CRM on the above time-to-event endpoints. PFS and OS were expressed by Kaplan-Meier method and compared by log-rank testing. Hazard ratios (HR) with 95% CIs were estimated using Cox regression models. Results: Out of 248 patients receiving maintenance therapy, CT and MRI scans of 211 patients were centrally evaluable (FU/FA+ Pmab, n = 106; FU/FA alone, n = 105). At baseline, 50.1% of the patients were diagnosed with &gt; 10 CRM. Median size of the largest CRM was 45 mm. Number of CRMs n≤10 was associated with favorable PFS, while both, number n≤10, and size of largest CRM ≤50mm correlated with favorable OS compared to n &gt; 10 and size of largest CRM &gt; 50mm, respectively. In patients with &gt; 10 CRMs, and those with largest CRM sized &gt; 50mm, PFS of maintenance therapy was significantly superior with FU/FA+ Pmab compared to FU/FA alone (Table). Conclusions: Metastatic burden was found to be prognostic for PFS and OS of maintenance therapy. Additionally, number and largest size of CRMs proofed predictive of PFS of maintenance therapy with Pmab, the primary endpoint of the trial. Patients with high metastatic burden at baseline appear to benefit particularly from Pmab-containing maintenance therapy. Clinical trial information: NCT01991873 . [Table: see text]
Endoscopist volume and the quality of colonoscopy of the Korean National Cancer Screening Program.
Authors: Dong Jun Kim, Nan-He Yoon, Seongju Kim, Ji Eun Kim, Hooyeon Lee
Journal: Journal of Clinical Oncology (2023)

6627 Background: The Korean government established the National Cancer Screening Program (KNCSP). The KNCSP has provided annual faecal immunochemical test (FIT) for adults aged 50 years or older, and colonoscopy or a double-contrast barium enema test to those with positive results from the FIT. High-quality screening colonoscopy is mandatory to achieve maximum possible CRC prevention. The case volume has been shown to correlate with outcomes in surgical specialties. In contrast, relevant data on colonoscopy is limited. This study aimed to assess the quality indicators of organized CRC screening according to annual colonoscopy volume using KNCSP data. Methods: We used the KNCSP data from 2018 to 2020, which accounted for 378,354 colonoscopy examinations. We used cancer registration data of an extended health insurance program using ICD-11 codes (C18-20). A total of 12,109 CRC patients were registered within 1 year of the date of colonoscopy. We calculated the annual number of colonoscopy examinations by an individual endoscopist. We excluded endoscopists who had a very low or high number of examinations with the highest 1% or lowest 1% as outliers. The final number of endoscopists was 16,552 and colonoscopy examinations were 331,231 during 2018–2020. The annual colonoscopy volume by individual endoscopists was divided into four groups (2–12, 13–24, 25–36, and 37 or more examinations). Multiple linear regression analysis was performed to confirm the association between test accuracy indicators and colonoscopy frequency using a generalized linear model (GLM). We calculated the estimates of the rates for each indicator by adjusting the year. Results: The positive and false positive rates, sensitivity, specificity, and positive predictive value were 4.09%, 1.07%, 83.53%, 98.93%, and 74.68%, respectively. The cancer detection and interval cancer rates were 30.53‰ and 6.29‰, respectively. Quality indicators were related to the annual colonoscopy volume of the endoscopist. Endoscopists with a higher annual colonoscopy volume were more likely to have higher sensitivity, specificity, and positive predictive value than those with a lower annual colonoscopy volume. Endoscopists with higher annual colonoscopy volumes were more likely to have lower positive rates, cancer detection rates, false positive rates, and interval cancers rate than those with lower annual colonoscopy volumes. Conclusions: This study found that the annual volume of colonoscopy examinations was associated with better colonoscopy quality in an organized CRC screening program. A high colonoscopy load could be a sign of substantial experience and lead to better outcomes, as has been shown for surgery. The relationship between quality indicators and case volume is logical and plausible; therefore, more research is required to determine the number of cases that need to be performed in a year to adequately maintain high colonoscopy quality.
The primary endpoint analysis of SCARLET study: A single-arm, phase II study of sotorasib plus carboplatin-pemetrexed in patients with advanced non-squamous, non-small cell lung cancer with KRAS G12C mutation (WJOG14821L).
Authors: Shinya Sakata, Hiroaki Akamatsu, Koichi Azuma, Takehiro Uemura, Yuko Tsuchiya-Kawano, Hiroshige Yoshioka, Mitsuo Osuga, Yasuhiro Koh, Satoshi Morita, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2023)

9006 Background: Efficacy and safety of sotorasib in combination with platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous, non-small cell lung cancer (non-Sq, NSCLC) has not been investigated. Methods: In this single-arm, phase 2 study, chemotherapy-naïve, advanced non-Sq, NSCLC patients with KRAS G12C mutation were enrolled. Participants were treated with sotorasib 960mg, QD plus carboplatin (AUC 5)/pemetrexed 500mg/m 2 for four cycles, followed by sotorasib plus pemetrexed until disease progression. The primary endpoint was overall response rate (ORR) by independent review. The secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Using plasma samples, next-generation sequencing analysis was done at baseline, 3 weeks and disease progression. Regarding statistical consideration, the threshold and the expected ORR were set as 40% and 65%, respectively with one-sided α = 0.1, and β = 0.1, the required sample size was 28 cases (Simon’s two-stage design). A total of 30 cases was planned to take into account the possibility of a few dropped or ineligible cases. This study was funded by AMGEN Inc. and Trial identification no. is jRCT2051210086. Results: Between Oct 2021 and Jul 2022, 30 patients were enrolled. Twenty-nine and 27 were analyzed for safety and efficacy, respectively. Of those, median age was 70, male/female: 25/5, never-/smoker: 1/29, ECOG performance status: 0/1 11/19 and PD-L1 expression level: ≥50%/1-49%/&lt;1% 15/10/5. The primary endpoint, ORR by independent review was 88.9% (80%CI 78.5-94.8%). Median PFS was not reached mainly due to shorter follow-up period (median 4.2 months) and PFS rate at 6 months was 61.2%. OS rate at 6 months was 87.0%. Subgroup analysis revealed that ORR did not differ by PD-L1 expression level (≥50%/1-49%/&lt;1%: 76.9%/77.8%/80.0%, respectively). Common adverse events were anemia, neutrophil count decreased, nausea and platelet count decreased. Grade≥3 AEs were mostly hematological toxicities, but one treatment-related death (pneumonia) occurred. At baseline, 70% of plasma samples were positive for KRAS G12C and most common co-occurring mutation was TP53 (50%). At 3 weeks, plasma KRAS G12C disappeared among 60% of patients. Conclusions: Sotorasib in combination with CBDCA/PEM demonstrated favorable ORR and tolerability in advanced non-Sq, NSCLC patients with KRAS G12C mutation. Clinical trial information: jRCT2051210086 .
Efficacy and safety in unresectable hepatocellular carcinoma with VP4 tumor embolus using sinilimab plus bevacizumab: A retrospective analysis of real-world evidence.
Authors: Jiamin Cheng, Bowen Chen, Xinfeng Zhang, Guodong Su, Caiyun Peng, Jin Lei, Lingxiang Yu, Yinyin Li, Yinying Lu
Journal: Journal of Clinical Oncology (2023)

e16156 Background: Recently, sinilimab plus bevacizumab has shown promising effects on unresectable hepatocellular carcinoma (uHCC) in ORIENT-32. However, its efficacy and safety in uHCC patients with VP4 cancer embolus remained unclear. Methods: In this retrospective study, uHCC patients with VP4 tumor embolus who received first-line sinilimab plus bevacizumab were consecutively enrolled. We also included similar patients who were treated with first-line sorafenib as comparison. Main efficacy endpoint was overall survival (OS), following progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR) to be secondary endpoints, evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: Total 43 eligible patients were enrolled, with 15 in sinilimab plus bevacizumab arm (arm 1) and the other 28 in sorafenib arm (arm 2). No statistical differences were found in etiology, liver function and performance status. At data cut-off at February 2023, median PFS in arm 1 and arm 2 were 3.7 (95%CI: 1.2-6.2) and 3.8 (95%CI:3.1-4.5) months, following ORR and DCR were 6.7% &amp; 46.7% and 7.1% &amp; 35.7%. OS in arm 1 was not matured and in arm 2 was 16.1 (11.1-21.1). Not any difference was detected among all efficacy endpoints. AEs happened among almost all patients. But nobody died of AEs. Conclusions: Efficacy and safety of sinilimab plus bevacizumab in uHCC patients with VP4 tumor embolus was similar with sorafenib, which needs to be further confirmed. [Table: see text]